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David Camenisch, MD/MPH PAL Conference Jackson, WY May 5, 2012 Pediatric Bipolar Disorder May 5, 2012 PAL Conference Slide 2 Cody (RR 2.5) - History 6 year old mixed-race (NA/AA) boy new to your practice ADHD diagnosis at age 4. On and off stimulants for 2 years. Has been tried on both methylphenidate and amphetamine preparations. They tend to work for a while but then things go back to normal. He has always been moody. Struggling at school socially but really smart. Per mom, He reads real history books and remembers everything. May 5, 2012 PAL Conference Slide 3 Cody Presentation Mom thinks he is bipolar. She just got diagnosed and medications have really helped her. Mom says she cant control him at home. A little better with moms boyfriend of who has been in and out of the picture for 2 years. Actually, mom just stopped stimulants because she heard they can make things worse if your kid has bipolar. She thinks he is doing better. She asks you to prescribe something to treat his bipolar mood swings May 5, 2012 PAL Conference Slide 4 What To Do? What role should a primary care provider take regarding the question of child bipolar disorder? Psychoeducation? Referral? Treatment? How do you assess for childhood bipolar disorder? When does it make sense to Wait Prescribe a mood stabilizer? Refer to a therapist? Refer to a (child and adolescent) psychiatrist? May 5, 2012 PAL Conference Slide 5 Bipolar Is A Hot Topic Bipolar disorder in kids is much talked about Child Anxiety Disorder on Google 26,600,000 hits (3,120,000) Child Bipolar Disorder on Google 33,100,000 hits (4,370,000) (Camenisch 2012, Camenisch 2011) Child anxiety disorders are actually about 10 times more common than child bipolar disorder 40 fold increase in office visits for child bipolar disorder from 1994 to 2003 (Also 40-fold increase in diagnosis.) National Center for Health Statistics May 5, 2012 PAL Conference Slide 6 Frequency of Childhood Bipolar Very controversial Some assert a high frequency of all children have bipolar disorder The Bipolar Child by Papolos and Papolos Assert 1/3 of all children with ADHD States about 6% of all children are bipolar Is Your Child Bipolar by McDonnell and Wozniak States more than 3 million US kids have it Based on their estimates, incidence is 4%. May 5, 2012 PAL Conference Slide 7 Quoted Child Rates Dont Match Our Adult Knowledge Adult Lifetime prevalence rates of bipolar disorder 1 to 2% Greater diagnostic certainty with adults Bipolar disorder is a lifelong diagnosis need plausible explanation if pediatric bipolar is 3-6X > adult bipolar Lessons from Great Smoky Mountain data set child bipolar NOS bipolar adult Kids with bad mood swings cannot all have true bipolar disorder May 5, 2012 PAL Conference Slide 8 Why is diagnosis so challenging? Symptom overlap + high rates of co-morbidity Confounding developmental issues Environmental influences Limited ability of (many) children to verbalize emotions Many different expert opinions Influence of popular media/pharmaceutical industry Requires extensive history assessment of both current symptoms and past episodes (subject to recall bias.) May 5, 2012 PAL Conference Slide 9 DSM-IV TR (Hypo)Manic Episode Manic Episode 7 days + impairment, or hospitalization or psychosis Distinct period of abnormal and persistently elevated*, expansive or irritable mood Plus 3 (4 if irritable-only mood) of the following: Distractible Grandiose/inflated self-esteem* Decrease need for sleep (< 3 hrs) More talkative/pressured speech Indiscretions/risk taking Flight of ideas/racing thoughts Increased goal directed activities/PMA Hypomanic Episode 4 days. No hospitalizations. No impairment. May 5, 2012 PAL Conference Slide 10 Depressive Episode 5 or more of following in same 2 week period + depressed/irritable mood OR lost of interest/anhedonia Sleep Interest Guilt Energy (fatigue) Concentration Attention PMA/PMR (observable) Suicidal thoughts/feelings/behaviors Functional Impairment No Mixed Episode, R/O Substance, R/O GMC, R/O Bereavement May 5, 2012 PAL Conference Slide 11 Diagnosis of Mood Disorders Current None MDEHypoManicMixed Past NoneNo Dx MDDNo Dx BP1BP1 MDEMDDMDDBP2BP1BP1 HypoNo DxBP2BP, NOSBP1BP1 ManicBP1BP1BP1BP1BP1 MixedBP1BP1BP1BP1BP1 Remember to ask about past mood symptoms, otherwise bipolar will be misdiagnosed as depression. May 5, 2012 PAL Conference Slide 12 Bipolar, NOS DSM-IV TR Rapid alternation between manic and depressive symtpoms that do not meet duration criteria Recurrent hypomanic episodes w/o depressive symptoms Manic or mixed episode in context of thought disorder Hypomanic episodes w/ chronic depressive symptoms Hypomanic/manic symptoms but havent yet been able to rule out influence of substance use or general medical condition. May 5, 2012 PAL Conference Slide 13 Bipolar Disorder, NOS Contributes to the current bipolar epidemic Label often given to impulsive, aggressive kids Prognosis could be normal, MDD, or (rarely) true bipolar Diagnosis confused with: ADHD Depression Abuse (current and PTSD) Anxiety Disorders Disruptive Behaviors Disorders Reactive Attachment Disorder Intermittent Explosive Disorder May 5, 2012 PAL Conference Slide 14 Why is Bipolar, NOS so common? Broad Category/catch-all Not (yet) another more suitable diagnosis that captures complex behavioral picture (SMD, TDDD) Sounds better to us than I dont know Justifies the limited(medication) treatment options. If we give a child medicine as if bipolar, parents often report improvement Bipolar medicines have many non-specific effects All decrease impulsivity and aggression May 5, 2012 PAL Conference Slide 15 If not bipolar, then what? Depression Ongoing abuse/neglect Post-trauma symptoms or syndrome Environmental Instability (frequent change in living arrangement/primary care giver; parental mental illness) Disordered Attachment (RAD) Temperament Mismatch (Parent-Child Relational Problem) Anxiety (especially brief, episodic, reactive mood swings ) Disruptive Behavior Disorders (ADHD,ODD) Affective lability in context of autism spectrum disorder (co- morbidity versus core disorder attribution) May 5, 2012 PAL Conference Slide 16 Severe Mood Dysregulation (SMD) Clinical syndrome not a diagnosis (3.3% lifetime prevalence ages 9-19) chronically irritable children whose diagnosis is in doubt. (Often the Bipolar, NOS crew) IS real and confers risk of psychopathology down the line, but is NOT bipolar disorder (also not Axis II) Presence of SMD increases risk of depressive disorder and GAD at 20 year follow-up. Stringaris et al, 2010 May 5, 2012 PAL Conference Slide 17 Bipolar Disorder Frequency Depends On Where You Look Prevalence of true adolescent bipolar 0.6% of high school students 1% in general outpatient practice 6 % of child psychiatry outpatients (CMHC) 22% incarcerated adolescents 26-34% of child psychiatry inpatients manic symptoms (1996-2004 CDC survey of discharge diagnosis) Youngstrom et al, CAPC Vol 18 May 5, 2012 PAL Conference Slide 18 Cody The Questions Test out whether un/under-treated ADHD (havent found right medication, right dose; hasnt had behavioral help, parenting support) or do you need to consider mood disorder? Or co-morbidity (depression, anxiety, ODD) Ask for more detail than just labile moods (hyper- arousal)and wont listen (distractibility) How is his mood most of the day? What causes (if anything) his mood to change? When not upset, what does he look like? Can he pull out of it Does he listen when he is asked to do something he wants to do? May 5, 2012 PAL Conference Slide 19 Cody The Answers Mom says he never listens to me especially when asked to do chore/homework/go to bed. Goes into rages when doesnt get his way Throws things at mom, hits her. Says I hate you. Tried everything, even spanking, taking away the Xbox. With dad or other adults he behaves better. Some talking back, but manageable. Knows he needs to cool it or he going to get in trouble. May 5, 2012 PAL Conference Slide 20 Cody At School In 2 nd grade, teacher said he was not listening well in beginning of year, is better now In kindergarten he didnt follow rules well Performing at grade level Not having rages at school Generally more of a problem at home more than at school May 5, 2012 PAL Conference Slide 21 Cody Social History and Development Mom is primary caregiver. 1 younger brother, mom thinks she might be pregnant. No contact with dad. Left before Cody was born. Mom has few supports. Moms family and tribe disowned her and Cody because his father is AA. Developmental milestones were OK Read early. Very verbal. Reads anything about history and remembers everything. No in utero drug exposure identified. May 5, 2012 PAL Conference Slide 22 How to answer Moms Question if this is Bipolar Disorder? Difficult diagnosis (no tests) Diagnosis best made over time ; usually not point-in-time diagnosis --especially with chronic presentation Many different opinions, even among specialists Down side of labeling too early If you think NOT bipolar, continue with Psycho-education. (Non-specific nature of mood swings and irritability e.g. cough analogy) Reasonable to consider treatment depending on potential consequences. (Sx-driven versus dx-driven treatment*) May 5, 2012 PAL Conference Slide 23 Consider the large differential for each of these Mania symptoms in kids: Distractible Indiscretions/risk taking Grandiose Flight of ideas/racing thoughts Activity (goal directed) increase Sleep need decreased Talkative (pressured speech) Which can mimic ADHD symptoms? May 5, 2012 PAL Conference Slide 24 Manic symptoms versus ADHD (Kowatch et al, 2005) SymptomADHDPBD* Irritability72%98% Accelerated Speech82%97% Distractibility96%94% Unusual Energy95%100% * Pediatric Bipolar Disorder May 5, 2012 PAL Conference Slide 25 Diagnostic Perspective Experience with adult mania helps, but can be challenging to translate to kids. (Different patterns of diagnosis between Adult and C&A psychiatrists?) Compare child to a prototypic manic patient Pressured speech -- not just talkative Having no doubt about their grandiose ideas -- impaired reality testing/lack of insight) Thought process is fast and jumping around Episodes that most commonly last days not minutes or hours Little need for sleep (versus poor sleep.) May 5, 2012 PAL Conference Slide 26 Look for Episodes and Patterns Individual episodes represent a clear departure from baseline with some hallmark symptoms Hopefully, the presence of hallmark symptoms will help distinguish irritable mania from irritable depression The correct mood diagnosis (and treatment) requires establishing the pattern of mood episodes, not just presenting (current) episode. May 5, 2012 PAL Conference Slide 27 Rapid Cycling Controversy Typical adult pattern is episodic. Rapid cycling is rare in adult bipolar populations. Kids are more reactive and more common to get story of rapid cycling. Consider rapid cycling in kids if there is no trigger identifiable for the mood changes Where many episodes become static, chronic mood state is controversial. ADHD plus irritability should not generate a bipolar diagnosis Youth with BP do spend more time cycling and have more changes in mood polarity that adult populations. (Birmaher et al, 2006) May 5, 2012 PAL Conference Slide 28 Chronic versus Episodic Irritability Objective: Test validity of distinction between chronic and episodic irritability. (Central debate in pediatric bipolar) Method: Community sample of 776 children and adolescents interviewed at 3 points in time (T0, T2y, T7y). Irritability rating scales used to tease out chronic versus episodic irritability. Association with age, gender and diagnosis were examined. (Liebenluft et al, 2006) May 5, 2012 PAL Conference Slide 29 Chronic vs Episodic Irritability Those with episodic irritability were more likely than those with chronic irritability to have: A parent diagnosed with Bipolar Disorder Experienced elation and/or grandiosity More symptoms of mania Psychotic symptoms Had a depressive episode Made a suicide attempt (Liebenluft et al, 2006) May 5, 2012 PAL Conference Slide 30 Irritability and Later Psychopathology Chronic irritability at TI - associated with ADHD at T2 and depression at T3 Episodic Irritability associate with simple phobia at T2 and mania at T3 Conclusions: - Episodic and chronic irritability are distinct constructs. - Episodic irritability is associated with bipolar disorder and confers higher risk of future manic episodes than chronic irritability. (Liebenluft et al, 2006) May 5, 2012 PAL Conference Slide 31 Irritability Controversy Geller: Irritability is not diagnostic of PBD; it is very common and shows high sensitivity, but poor specificity for PBD Wozniak: irritability may be primary mood symptom; episodicity not relevant. Leibenluft: In diagnosing PBD, episodic irritability is more suggestive of PBD than is chronic irritability Hunt/Birmaher episodic irritability alone can represent manic phase of illness; irritable-only mania exists but is rare; more common in younger children. (COBY). May 5, 2012 PAL Conference Slide 32 Look for Hallmark Symptoms Increased specificity More likely bipolar Elation Hyperactivity Grandiosity Hypersexuality Decreased need for sleep May 5, 2012 PAL Conference Slide 33 Bipolar Diagnostic Aides Rating Scales Young Mania Rating Scale Useful for monitoring symptoms over time Not a diagnostic tool (very low specificity) DISC or KSADS Used in research, have flaws Impractical for your office practice Rating scales are too misleading to recommend for diagnostic use and are intentionally excluded from the PAL guide. May 5, 2012 PAL Conference Slide 34 Cody Rage episodes seem directed mostly at mom, and moms attempts to set limits at home Mood changes occur mostly in response to frustrations There are not any hallmark symptoms of grandiosity, euphoria, hypersexuality No history of days-long episodes He is very young to diagnose as bipolar May 5, 2012 PAL Conference Slide 35 What about Family History? Mom says she has been diagnosed with bipolar and his uncle is bipolar, just like him Avoid overcalling a positive family history many adults who call themselves bipolar may not have that illness first degree relative bipolar disorder, increases OR by 5 second degree relative bipolar, increase OR by 2.5 given a generous prevalence of 2% bipolar in the population, most children of a bipolar parent (~90%) will not have bipolar disorder Youngstrom E & Duax J, JAACAP 44:7, 2005 May 5, 2012 PAL Conference Slide 36 Looking back at adult bipolar. Several studies have asked adults with bipolar about onset of their symptoms retrospectively Bipolar adults look back and note symptoms became bipolar- like in their teen years (50-66%) Many bipolar adults had major depression episodes as children The younger the childs first major depression, the more likely bipolar disorder is in the future May 5, 2012 PAL Conference Slide 37 What if a Bipolar Child Really is Bipolar? Though rare in a PCP practice, becomes more likely the older the child. Typical pattern is early onset depression, and during teenage years getting first symptoms of mania. Expect mood episodes. COBY study established validity of episodic course. Assemble a team. Real deal bipolar disorder is a big problem. May 5, 2012 PAL Conference Slide 38 Course Of True Bipolar Disorder Suicidalilty up to 15% eventually complete suicide Substance Abuse in up to 60% Anxiety disorders in up to 50% Psychotic features in up to 50% Relationship Disruptions Work Disruptions Hospitalizations Stern TA and Herman JB, 2004 May 5, 2012 PAL Conference Slide 39 Bipolar Treatment If clear manic episodes, strongly recommend get them to child psychiatrist Management difficult because: High rate of substance abuse High rate of medication non-compliance Even with medication, recurrences happen High rates of family disruption from the illness Suicidal behavior is common Brent et al, 1988, 1993 May 5, 2012 PAL Conference Slide 40 If No Child Psychiatrist Can Assume Care, Then What? Get collateral evaluations to help establish correct diagnosis Strongly advise against rushing to offer diagnosis of bipolar disorder. Seek consultant advice on medication (when they are appropriate to consider) Preferred model of care: MH specialist is primary prescriber PCP is a partner in the treatment team Call the Provider Access Line. Sometimes PCP is left holding the bag May 5, 2012 PAL Conference Slide 41 Bipolar Treatments (for when you are left holding the bag) Atypical antipsychotics Mood Stabilizers Combination therapy Antidepressants if used cautiously Family therapy (support/education/adherence) Sleep hygeine Psychotherapy for: depression treatment coping skills supporting medication treatment adherence May 5, 2012 PAL Conference Slide 42 Bipolar Medications May 5, 2012 PAL Conference Slide 43 What Is A Mood Stabilizer? Includes both atypical anti-psychotics and anti-epileptic drugs (AEDs) Generic term clarify what they mean when taking history and what you mean when proposing treatment. FDA does not recognize this term As relates to treatment of bipolar disorder, ideally treats both depressive and manic episodes as well as prevents recurrence of mood episodes. Since no one compound does this well, multiple meds are often used together (but little evidence base to support it.) May 5, 2012 PAL Conference Slide 44 Mood Stabilizers are Non-Specific to PBD Maladaptive aggression Mental retardation (lithium, risperidone) Autism (risperidone, aripiprazole) Conduct Disorder (risperidone, valproic acid, lithium) Seizure Disorders kindling hypothesis; neuroprotective effects in mood disorders (lithium) Depression (risperidone, aripiprazole, quetiapine, lamotrigine) Psychosis (primary, mood disorder, delirium) OCD (refractory) PTSD (intrusive thoughts) May 5, 2012 PAL Conference Slide 45 Pharmacotherapy of Pediatric Bipolar (Liu et al, JAACAP 2011) May 5, 2012 PAL Conference Slide 46 Positive Randomized Trials Blinded RCT knowledge base in kids is low Aytpical anti-psychotics Olanzapine Aripiprazole (2) Quetiapine (3) Risperidone (1) AEDs Divalproex sodium (Depakote) Li (maintenance) May 5, 2012 PAL Conference Slide 47 Atypical Antipsychotics risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone 11 OTs with 53% response rate 8 DBRCTs with 66% response rate N = 1474 That DBRCTs showed greater efficacy than placebo is encouraging and noteworthy Better tolerated than AEDs as a group. May 5, 2012 PAL Conference Slide 48 Risks common to all Atypical Antipsychotics (Correll, JAACAP. 2008) Sedation (olanzapine, quetiapine) Tardive Dyskinesia (0.4% annual incidence) Increased Cholesterol/ Triglycerides (olanzapine) Akathesia (aripiprazole) (youth quetiapine, risperidone >the rest) Neuroleptic Malignant Syndrome May 5, 2012 PAL Conference Slide 49 Atypical Heterogeneity May 5, 2012 PAL Conference Slide 50 Adverse and Therapeutic Effects of Occupancy and Withdrawal (Correll, JAACAP. 2008) May 5, 2012 PAL Conference Slide 51 Risperidone (Risperdal) PROS QD-BID dosing (T = 20 hours) FDA for mania > 10 years old, irritability/aggression in ASD Multiple dosage forms (liquid, dissolving tab, tabs, depot) Low doses ( Slide 52 Aripiprazole (Abilify) PROS QD-BID dosing ( T=75 hrs) But kids may do better BID FDA for mania (>10 yrs) and limited RCT support Mixed agonist/antagonist (less dystonia/EPS) Often less sedation CONS Limited dosage forms Misperception of less weight gain/metabolic SE Agitation/activation not uncommon Higher rates of akithesia Long T -may take longer to see impact of changes May 5, 2012 PAL Conference Slide 53 Quetiapine (Seroquel) PROS Lower potency - may be experienced as milder FDA approval (>10 years old)/limited RCT evidence Effective anxiolytic Cross indication for bipolar and unipolar depression CONS Short half-life (T = 6 hours); multiple daily dose; mixed results w/ XR preparation Large tablets - may be hard to swallow Effective sleep aide (high risk, high cost sleep aide) Cataract risk May 5, 2012 PAL Conference Slide 54 Olanzapine (Zyprexa) PROS QD-BID dosing (T = 30 hours) FDA approval (> 13 years) and limited RCT evidence Multiple dosage forms (tablets, oral disintegrating, IM) Very effective for acute stabilization of mania and psychosis CONS Weight gain (dose related, less of plateau than others) High rates of metabolic side effects Sedation common May 5, 2012 PAL Conference Slide 55 Ziprasidone (Geodon) PROS Often less sedating Most weight neutral Fewer metabolic side effects Unique receptor profile CONS BID-QID dosing (T = 7 hrs) No FDA approval for pediatric mania No pediatric RCT support Concern for EKG changes has lowered its usage May 5, 2012 PAL Conference Slide 56 Monitoring for all atypical antipsychotics: AIMS exam at baseline and Q6months due to risk of tardive dyskinesia. Warn of dystonia risk. Weight checks, fasting glucose/lipid panel Q6months at minimum. May 5, 2012 PAL Conference Slide 57 Anti-convulsants Lithium (Li), divalproex sodiumm(VPA), carbamazepine (CBZ) 14 OTs (41% response rate) 6 RCTs (40 % response rate) n = 915 Only RCTs for divalproex sodium No RCTs for Li or CBZ Lamotrigine, oxcarbazepine, topiramate 3 OTs (43% response rate) 2 RCTs (39%) n = 244 May 5, 2012 PAL Conference Slide 58 Lithium PROS FDA approved for mania >12 years Some evidence in refractory depression Anti-suicide properties Some EB dosing guidelines (adjust for age/GFR) CONS Narrow therapeutic index (close monitoring for toxicity w/ illness/dehydration; no NSAIDs) Usually best in combination, so committing to polypharmacy if you start here (best w/ atypical or VPA) SE in therapeutic range similar to early toxicity (tremor, diarrhea) SE often limit use (weight gain, acne, GI); HS dosing can minimize Hard to predict who will respond No evidence for maintenance treatment /slow anti-manic effects May 5, 2012 PAL Conference Slide 59 Early Signs May 5, 2012 PAL Conference Slide 60 Valproic Acid (Depakote) PROS Single daily dosing can be effective (Depakote ER) Can be useful for maladaptive/non-specific aggression Studies suggest helpful, usually in combination CONS Requires blood draws (levels, LFTs, amylase, CBC) Risk of hepatotoxicity (highest in first 6 months) High side-effect burden (weight gain, GI, tremor, sedation, rash) Less ideal for females (risk of birth defects (NTD), PCOS) May 5, 2012 PAL Conference Slide 61 Depakote How well does it work? Fair, usually works best in adolescents in combination with an antipsychotic (better than either one alone) Some RCTs have suggested that it works better than lithium on acute manic symptoms Broad effects: also used for externalizing behavior disorders, conduct disorder Lost in head-to-head trial with quetiapine Similar long-term stabilizing effect to Lithium after stabilization with both divalproex and lithium DelBello MP et al, 2002, 2006 Bowden C et al, 2004 Rana M et al, 2005 Findling, R et al 2005 May 5, 2012 PAL Conference Slide 62 Carbamazepine (Tegretol) PROS Some empirical supports for aggression 2 OTs Similar response rates as Li and VPA (38%) (Kowatch et al, 2005) CONS Drug/drug interactions (OCPs, Lithium) Blood draws to check levels (auto-induced metabolism) Weak evidence of benefit in bipolar (McClellan and Werry, 1997) Risk of aplasia and liver failure May 5, 2012 PAL Conference Slide 63 Hard to Compare Effectiveness 42 child outpatients with Bipolar 1 or 2, randomized to one of three open label treatments R Kowatch et al, 2000 May 5, 2012 PAL Conference Slide 64 Lamotrigine (Lamictal) PROS Bipolar depression treatment Less sedation and lower side effect profile in general CONS Not helpful for manic phase Requires monitoring of CBC and liver function Significant rash risk Slow titration (age >12) May 5, 2012 PAL Conference Slide 65 Oxcarbazepine (Trileptal) PROS FDA approval for adults bipolar disorder Weight neutral Less risks/side effects than carbamazepine Monitoring of levels not required CONS Levels do not correlate well with efficacy or toxicity Negative adolescent bipolar trial (Cochrane Review. Vasudev et al. 2008) Hyponatremia not uncommon May 5, 2012 PAL Conference Slide 66 Anticonvulsants Shown Not To Help In Adult Bipolar Disorder topiramate (Topamax) (1 negative pediatric trial) gabapentin (Neurontin) levetiracetam (Keppra) - can cause psychiatric symptoms zonisamide (Zonegran) pregabalin (Lyrica) felbamate (Felbatol) - can cause psychiatric symptoms May 5, 2012 PAL Conference Slide 67 Bipolar Take-Home Message Diagnosis of bipolar disorder made with relative confidence in the presence of manic (Bipolar I) or hypomanic (Bipolar II) episodes. It gets tricky after that. Mood episodes (all) involve distinct change from baseline with alternations in behavior and evidence of impairment. Bipolar diagnosis is a serious diagnosis that has a life-long course and many management challenges. True bipolar has high rates of morbidity and mortality. If suspected, strongly recommend involving a child and adolescent psychiatrist. If you, as PCP, are playing central role in management, check-in frequently to monitor side effects of medication(s) and surveillance of mood symptoms. May 5, 2012 PAL Conference Slide 68 Not-Bipolar Take-Home Message Currently, there is no single diagnosis for chronically dysregulated or irritable kids. Evidence is more suggestive of current and/or future depressive disorder. Kids with severe, non-episodic irritability differ from those with bipolar in course, family history and performance in many cognitive tasks linked to more severe psychopathology. Still a major role for parent support/training and mental health support. These kids can be draining and are high risk. There can be a role for medications to decrease maladaptive aggression and affective instability. May 5, 2012 PAL Conference Slide 69 At PCP level, recommend. keeping in mind many possible causes of mood swings and irritability. resisting temptation to label impulsive, difficult kids as bipolar. reminding yourself and parents who are struggling that most disruptive, irritable children do not have bipolar disorder but can still benefit from help. getting help with diagnostic and treatment questions as often as necessary. May 5, 2012 PAL Conference Slide 70 Selected Bibliography Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review and Meta-Analysis. Liu et al. JAACAP. August 2011. Practitioner Review: The Assessment of Bipolar Disorder in Children and Adolescents. Baroni et al. JCPP. 2009. Antipsychotic Use in Children and Adolescents:Minimizing Adverse Effects to Maximize Outcomes. Correll. JAACAP. January 2008. May 5, 2012 PAL Conference